Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy Plus Warfarin in Treating Patients With Prostate Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Supportive care, Treatment Closed 18 and over NCI MSKCC-00113 NCI-G01-1927, NCT00014352

Objectives

I. Determine the safety, efficacy, and durability of docetaxel and 
estramustine followed by doxorubicin and ketoconazole in patients with 
high-risk, androgen-independent prostate cancer.

II. Determine whether anticoagulation with warfarin can reduce the frequency 
of thromboembolic complications associated with estramustine in these patients.

Entry Criteria

Disease Characteristics:

Histologically confirmed prostate cancer

High risk as defined by any 2 of the following:
 Karnofsky performance status of 70-80%
 Lactate dehydrogenase greater than 200 U/mL
 Hemoglobin less than 13 g/dL

Prostate-specific antigen (PSA) at least 4 ng/mL

Progressive disease based on any 1 of the following:
 Rise in PSA level of at least 25% above baseline
  At least 3 determinations taken at weekly intervals OR
  At least 2 determinations taken at monthly intervals
 New or progressive soft tissue masses on MRI or CT scan
 Radionucleotide bone scan with new metastatic lesion(s)

Serum testosterone no greater than 30 ng/mL

If no prior surgical orchiectomy, castrate levels of serum testosterone must
be maintained with continuation of gonadotropin releasing hormone analogs

If receiving an anti-androgen, must show progression of disease after stopping
anti-androgen therapy

Prior/Concurrent Therapy:

Biologic therapy:
 Not specified

Chemotherapy:
 No more than 1 prior chemotherapy regimen

Endocrine therapy:
 See Disease Characteristics

Radiotherapy:
 No more than 1 prior course of palliative radiotherapy
 No more than 1 prior radioisotope therapy with strontium chloride Sr 89 or
  samarium Sm 153 lexidronam pentasodium

Surgery:
 See Disease Characteristics
 At least 4 weeks since prior major surgery

Patient Characteristics:

Age:
 18 and over

Performance status:
 See Disease Characteristics
 Karnofsky 70-100%

Life expectancy:
 Not specified

Hematopoietic:
 See Disease Characteristics
 WBC at least 3,000/mm3
 Platelet count at least 100,000/mm3

Hepatic:
 Bilirubin normal
 SGOT/SGPT no greater than 1.5 times upper limit of normal (ULN)

Renal:
 Creatinine no greater than 1.5 times ULN

Cardiovascular:
 No significant cardiovascular disease
 No New York Heart Association class III or IV heart disease
 No active angina pectoris
 No myocardial infarction within the last 6 months
 Ejection fraction at least 45% by echocardiogram or MUGA
 No prior hemorrhagic or thrombotic cerebral vascular accident
 No deep venous thrombosis

Pulmonary:
 No pulmonary embolism within the past 6 months

Other:
 No history of bleeding disorder or gastrointestinal bleeding that would
  preclude anticoagulation with warfarin
 No other concurrent malignancy except non-melanoma skin cancer or any
  curatively treated malignancy considered to be at less than 30% risk of
  relapse
 No severe infection
 No severe malnutrition
 No other serious medical illness that would preclude study

Expected Enrollment

A total of 50 patients will be accrued for this study within 1 year.

Outline

Regimen A: Patients receive oral estramustine 3 times daily on days 1-5 and 
docetaxel IV over 1 hour on day 3 weekly.  Patients also receive oral warfarin 
daily.  Treatment repeats every 4 weeks for a total of 2 courses in the 
absence of disease progression or unacceptable toxicity.

Regimen B: After completion of regimen A, patients receive doxorubicin IV over 
30 minutes weekly and oral ketoconazole twice daily.  Treatment repeats every 
4 weeks for a total of 2 courses in the absence of disease progression or 
unacceptable toxicity.

Patients are followed monthly until disease progression.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

William Kelly, DO, Protocol chair(Contact information may not be current)		Ph: 203-737-2572; 800-525-2225

Registry Information
Official Title		Phase II Trial Of Sequential Estramustine/Paclitaxel Followed By Doxorubicin/Ketoconazole In Patients With Androgen-Independent Prostate Cancer
Trial Start Date		2000-09-26
Registered in ClinicalTrials.gov		NCT00014352
Date Submitted to PDQ		2001-02-16
Information Last Verified		2002-07-01
NCI Grant/Contract Number		CA08748